To a large extent the physiological alterations that develop during shock are coordinated to preserve the steady states vital to survival (homeostasis). Thus studies of shock should provide insight into the mechanisms which constitute homeostasis. This information is applicable to a better understanding of illness as well as injury. While the physiological alterations induced by shock are relatively well described, their relationship to the metabolic processes upon which they are dependent for energy production has received only minimal attention. To study this relationship it is desirable to use a shock model in which the physiological adjustments and corresponding metabolic alterations can be viewed throughout the initial period of homeostatic response, the ensuing period of maximal homeostatic activity, and a terminal period of deterioration. Specific alterations require a more detailed analysis of isolated organs and tissues (e.g. glucose uptake by muscle, insulin activity, proteolysis). Many of these studies are applicable to man, after their relevance to the spectrum of homeostasis has been delineated in animals. It is proposed to study energy metabolism in relation to the maintenance and eventual deterioration of homeostatic physiological reactions during prolonged hypovolemic shock. To accomplish this goal, studies are planned in four areas: 1) The influence of nutrition on homeostasis during shock. 2) The effectiveness of insulin as a mediator of energy metabolism during successive stages of shock. 3) Intracellular oxygen delivery to mitochondria. 4) Development of isolated tissues as model systems for study of altered metabolism.